miR-503通过靶定IGF-1R基因抑制胃癌生长与侵袭

miR-503 Inhibits Cell Growth and Invasion by Targeting IGF-1R in Human Gastric Carcinoma

目的探讨miR-503在胃癌细胞生长及侵袭中的作用,并探索其相关分子机制。方法利用Realtime PCR检测人胃癌及癌旁组织miR-503及IGF-1R的mRNA表达情况。在人胃癌细胞系MGC-803和SGC-7901中瞬时转染miR-503模拟物和模拟物对照,运用平板克隆形成实验和Transwell侵袭实验检测miR-503的作用。在MGC-803和SGC-7901中转染IGF-1R干扰RNA和对照siRNA,利用Western blot检测IGF-1R蛋白表达情况,并进一步检测IGF-1R对细胞克隆形成和侵袭能力的影响。结果 miR-503在胃癌中呈现低表达(P<0.01),IGF-1R的mRNA呈现高表达(P<0.01)。与对照组细胞相比,转染miR-503模拟物的细胞克隆数目明显减少(P<0.01),发生侵袭的细胞也减少(P<0.01),IGF-1R蛋白水平降低。转染IGF-1R干扰RNA的细胞中IGF-1R蛋白水平较对照组降低,且克隆形成和侵袭能力较对照组明显降低(P<0.01)。结论 miR-503可以通过靶定IGF-1R基因调控胃癌细胞的生长和侵袭,发挥抑癌作用,具有作为胃癌分子治疗和预后靶标的潜能。

Objective In this study,we aim to detect the mechanism of miR-503 in gastric carcinoma cell growth and invasion.Methods Real-time PCR was performed to detect the expression of miR-503 and IGF-1R mRNA in gastric carcinoma tissues and adjacent tissues.MGC-803 and SGC-7901 cells were transfected with miR-503 mimics and control mimics,and cell growth and invasion abilities were tested by colony formation assay and transwell invasion assay.The cells were transfected with the IGF-1RsiRNA,and Western blot was used to detect the IGF-1Rexpression.Then,the cell colony formation and invasion abilities were determined in siRNA-transfected cells.Results Compared to adjacent tissues,miR-503 showed low expression in gastric carcinoma tissues（P〈0.01）,and IGF-1RmRNA was highly expressed（P〈0.01）.The number of colonies and invading cells in the cells with miR-503 mimics was significantly reduced（P〈0.01）.In addition,the cells with miR-503 mimics had a low protein level of IGF-1R.IGF-1Rexpression was knockdown by the IGF-1RsiRNA（P〈0.01）.Knocking down of IGF-1Rresulted in the inhibition of cell colony formation and invasion abilities（P〈0.01）.Conclusion miR-503 modulates gastric carcinoma cell growth and invasion by targeting IGF-1R.Our data suggest that miR-503 has immense potential as a miRNA-based therapeutic target for gastric carcinoma.